X-ray Parametric Down Conversion at the APS Synchrotron

We present measurements of X-ray Parametric Down Conversion at the Advanced Photon Source synchrotron facility. We use an incoming pump beam at 22 keV to observe the simultaneous, elastic emission of down-converted photon pairs generated in a diamond crystal. The pairs are detected using high count rate silicon drift detectors with low noise. Production by down-conversion is confirmed by measuring time-energy correlations in the detector signal, where photon pairs within an energy window ranging from 10 to 12 keV are only observed at short time differences. By systematically varying the crystal misalignment and detector positions, we obtain results that are consistent with the constant total of the down-converted signal

Multiple hypotheses explain variation in extra-pair paternity at different levels in a single bird family

Extra‐pair paternity (EPP), where offspring are sired by a male other than the social male, varies enormously both within and among species. Trying to explain this variation has proved difficult because the majority of the interspecific variation is phylogenetically based. Ideally, variation in EPP should be investigated in closely related species, but clades with sufficient variation are rare. We present a comprehensive multifactorial test to explain variation in EPP among individuals in 20 populations of nine species over 89 years from a single bird family (Maluridae). Females had higher EPP in the presence of more helpers, more neighbours or if paired incestuously. Furthermore, higher EPP occurred in years with many incestuous pairs, populations with many helpers and species with high male density or in which males provide less care. Altogether, these variables accounted for 48% of the total and 89% of the interspecific and interpopulation variation in EPP. These findings indicate why consistent patterns in EPP have been so challenging to detect and suggest that a single predictor is unlikely to account for the enormous variation in EPP across levels of analysis. Nevertheless, it also shows that existing hypotheses can explain the variation in EPP well and that the density of males in particular is a good predictor to explain variation in EPP among species when a large part of the confounding effect of phylogeny is excluded

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope

Sex-specific effects of the local social environment on juvenile post-fledging dispersal in great tits

An individual’s decision to disperse from the natal habitat can affect its future fitness prospects. Especially in species with sex-biased dispersal, we expect the cost–benefit balance for dispersal to vary according to the social environment (e.g., local sex ratio and density). However, little is known about the social factors affecting dispersal decisions and about the temporal and spatial patterns of the dispersal process. In our study, we investigated experimentally the effects of the social environment on post-fledging dispersal of juvenile great tits by simultaneously manipulating the density and sex ratio of fledglings within forest plots. We expected young females in the post-fledging period mainly to compete for resources related to food and, as they are subordinate to males, we predicted higher female dispersal from male-biased plots. Juvenile males compete for vacant territories already in late summer and autumn; thus, we predicted increased male dispersal from high density and male-biased plots. We found that juvenile females had a higher probability to leave male-biased plots and had dispersed further from male-biased plots in the later post-fledging phase when juvenile males start to become territorial and more aggressive. Juvenile males were least likely to leave male-biased plots and had smallest dispersal distances from female-biased plots early after fledging. The results suggest that the social environment differentially affected the costs and benefits of philopatry for male and female juveniles. The local sex ratio of individuals is thus an important social trait to be considered for understanding sex-specific dispersal processes

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's) : an ARChiVe Cohort Study

OBJECTIVE: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons. RESULTS: In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n\u2009=\u200948) or GPA (n\u2009=\u2009183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil. CONCLUSION: Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding

Carotenoid-Based Ornaments of Female and Male American Goldfinches (Spinus tristis) Show Sex-Specific Correlations with Immune Function and Metabolic Rate

Conspicuous ornamentation has been linked to immunological and physiological condition in males of many species. In species where both sexes are ornamented, it is unclear whether the signal content of ornaments differs between males and females. We examined the immunological and physiological correlates of carotenoid-based bill and plumage ornamentation in American goldfinches Spinus tristis, a species in which bright orange bills are sexually monomorphic but yellow plumage is sexually dimorphic during the breeding season. Because bill color is dynamic over short periods while plumage color is static over longer time frames, we tested whether these signals have the potential to provide temporal information about immunity and condition. In both sexes, bill color (but not plumage color) was negatively related to leukocyte differential, a measure of recent stress, while plumage color (but not bill color) was positively related to resting metabolic rate. In females, bill color also positively correlated with immunoglobulin Y, a component of acquired immunity, while plumage color positively predicted natural antibody levels, a component of innate immunity. In males, neither bill color nor plumage color predicted immune function, suggesting that the mechanisms underlying these signals vary with sex. Our results demonstrate that dynamic signals such as bill coloration do not merely reflect the same information provided by static signals but that these two classes of signal provide information about different temporal aspects of phenotypic quality. Furthermore, our results indicate that a signal expressed in both sexes has the potential to provide different information depending on the sex of the bearer